WO2000021512A2 - Composition et procede pour le traitement d'allergies - Google Patents

Composition et procede pour le traitement d'allergies Download PDF

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Publication number
WO2000021512A2
WO2000021512A2 PCT/US1999/021437 US9921437W WO0021512A2 WO 2000021512 A2 WO2000021512 A2 WO 2000021512A2 US 9921437 W US9921437 W US 9921437W WO 0021512 A2 WO0021512 A2 WO 0021512A2
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WO
WIPO (PCT)
Prior art keywords
antagonist
pharmaceutical composition
pharmaceutically acceptable
acceptable derivative
neurokinin
Prior art date
Application number
PCT/US1999/021437
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English (en)
Other versions
WO2000021512A3 (fr
Inventor
Robert G. Aslanian
John J. Piwinski
Original Assignee
Schering Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Schering Corporation filed Critical Schering Corporation
Priority to JP2000575488A priority Critical patent/JP2002527381A/ja
Priority to EP99949707A priority patent/EP1117405A2/fr
Priority to CA002346227A priority patent/CA2346227A1/fr
Priority to AU62526/99A priority patent/AU6252699A/en
Publication of WO2000021512A2 publication Critical patent/WO2000021512A2/fr
Publication of WO2000021512A3 publication Critical patent/WO2000021512A3/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/04—Drugs for disorders of the respiratory system for throat disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/14—Decongestants or antiallergics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention generally relates to compositions and methods for treating allergic rhinitis and other respiratory diseases. It specifically discloses compositions which comprise combinations of antagonists of neurokinin receptors and antagonists of histamine receptors, and methods for treating the above-noted diseases with such compositions.
  • Neurokinin receptors such as the NK, and the NK 2 receptors are found in the central nervous system, the circulatory system, and the peripheral tissues of mammals, and are involved in a variety of biological processes. Antagonists of the neurokinin receptors are, therefore, expected to be useful in the treatment or prevention of various mammalian diseases such as, for example, pulmonary disorders such as asthma, cough, bronchospasm, chronic obstructive pulmonary diseases, and airway hyperactivity; skin disorders and itch, for example, atopic dermatitis, and cutaneous wheal and flare; neurogenic inflammatory diseases such as, arthritis, migraine, nociception; CNS diseases such as anxiety, emesis, Parkinson's disease, movement disorders and psychosis; convulsive disorders, renal disorders, urinary incontinence, ocular inflammation,, inflammatory pain, and eating disorders such as food intake inhibition; allergic rhinitis, neurodegenerative disorders, psoriasis, Huntington's disease, depression and various disorders such as Crohn'
  • NK, receptors have been reported to be involved in microvascular leakage and mucus secretion, and NK 2 receptors have been associated with smooth muscle contraction, making NK, and NK 2 receptor antagonists especially useful in the treatment and prevention of asthma.
  • NK, and NK 2 receptor antagonists have been reported such as, for example, in U.S. patents 5,798,359; 5,795,894; 5,789,422; 5,783,579; 5,719,156; 5,696,267; 5,691 ,362; 5,688,960; 5,654,316; and in "Recent Advances in Neurokinin Receptor Antagonists", by C. J. Ohnmacht Jr., et al, Annual Reports in Medicinal Chemistry, A. M.
  • H 3 receptor is most abundantly distributed in the CNS, and in lesser amounts in peripheral tissues.
  • the H 3 receptor is considered an important general neuroregulatory mechanism for various physiological processes, not only in the CNS but in peripheral tissues as well.
  • a discussion of the H 3 receptor and antagonists therefor can be found in J. G. Phillips et al, Annual Reports in Medicinal Chemistry, J. Bristol, ed., 33, 31 -40 (1998).
  • the afore-mentioned objective and other objectives and desires are addressed by the present invention which, in one embodiment, provides a composition for treating and preventing allergic rhinitis and other respiratory diseases such asthma, cough, wheezing and the like.
  • the inventive composition comprises: (i) a therapeutically effective amount of at least one neurokinin antagonist; (ii) a therapeutically effective amount of at least one H 3 antagonist and (iii) a therapeutically effective amount of at least one H 1 antagonist.
  • One or more of the antagonists may be substituted by a pharmaceutically acceptable derivative such as salt, ester, and the like, if so desired.
  • the composition may additionally contain a pharmaceutically acceptable carrier, a decongestant (such as, for example, pseudoephedrine), a cough suppressant (such as, for example, dexrtomethorphan), expectorant (such as, for example, guaifenesin), analgesics (such as, for example, aspirin, ibuprofen and acetaminophen) or mixtures thereof.
  • a decongestant such as, for example, pseudoephedrine
  • a cough suppressant such as, for example, dexrtomethorphan
  • expectorant such as, for example, guaifenesin
  • analgesics such as, for example, aspirin, ibuprofen and acetaminophen
  • the amount of the neurokinin antagonist content in the inventive composition is about 1-1 ,000 milligrams, preferably about 10-500 milligrams, and typically about 50-200 milligrams.
  • the amount of the H 3 antagonist is generally about 1 -1 ,000 milligrams, preferably about 1 -500 milligrams, and typically about 1 -50 milligrams.
  • the amount of the H, antagonist is generally about 1 -200 milligrams, preferably about 1 -100 milligrams, and typically about 2-10 milligrams.
  • the invention further provides a method for treating asthma and allergic disorders, sneezing, itching runny nose, nasal congestion, redness of the eye, tearing, itching of the ears or palate, sinusitis, and coughs associated with postnasal drip symptoms in a mammalian organism in need of such treatment comprising administering a pharmaceutical composition as described above.
  • the present invention discloses pharmaceutical compositions that are useful in treating and preventing allergic rhinitis, asthma and related disorders.
  • the composition comprises, in combination, a therapeutically effective amount of at least one neurokinin antagonist, a therapeutically effective amount of at least one H 3 antagonist and a therapeutically effective amount of at least one H, antagonist.
  • One or more of the antagonists may be substituted by a pharmaceutically acceptable derivative such as salt (such as, for example, hydrochloride), ester, and the like.
  • neurokinin antagonists that are currently known are useful in the practice of the present invention.
  • useful neurokinin antagonists include, for example, those belonging to the chemical class of oximes, hydrazones, piperidines, piperazines, aryl alkyl amines, hydrazones, nitroalkanes, amides, isoxazoiines, quinolines, isoquinolines, azanorbomanes, naphthyridines, benzodiazepines and the like.
  • Preferred NK antagonists are those disclosed in the above- noted U.S.
  • X is -O-; -NR 6 -; -N(R 6 )CO-; or -CO-NR 6 -;
  • T is R 4 -aryl; R 4 -heteroaryl; R 4 -cycloalkyl; or R 2 -bridged cycloalkyl;
  • G is H; R 4 -aryl; R 4 -heteroaryl; COR 6 ; CO 2 R 6 ; CONR 6 R 7 ; CN; OCOR 6 ; S0 3 R 2 ;
  • R 2 and R 3 are independently H or C,-C 6 alkyl
  • R 4 and R 5 are independently 1 , 2 or 3 substituents independently selected from OR 2 , OC(0)R 2 , OC(O)NR 6 R 7 , C C 6 alkyl, H, halogen, CF 3 , C 2 F 5 , or OCF 3 ; and R 6 and R 7 are independently selected from H or C C 6 alkyl, with the proviso that when R 6 and R 7 are part of NR 6 R 7 then said NR 6 R 7 may form part of a C 5 -
  • C 5 -C 6 ring may contain substituents on said ring with said substituents being selected from the group consisting of hydrogen, halogen, -OR 6 and -COOR 6 .
  • Particularly preferred neurokinin antagonists are those disclosed in the above-mentioned U.S. patents and belonging to the general formula:
  • stereoisomers thereof. More particularly preferred are the stereoisomers with the general formula:
  • R is H, CH 2 CONH 2 , CH 2 CONHMe, CH 2 CONMe 2 or
  • H 3 receptor antagonists cannot be easily classified chemically.
  • Illustrative H 3 receptor antagonists useful in the practice of the present invention include, without limitation, thioperamide (technical name: N-cyclohexyl-4-(1H-imidazol-4-yl)-1- piperidinecarbothioamide, CAS Registry Number: 106243-16-7), impromidine (technical name: N-[3-(1 H-imidazol-4-yl)propyl]-N'-[2-[[(5- methyl-1 H-imidazol-4-yl)methyl]thio]ethyl]guanidine, CAS Registry Number: 65573-02-6), burimamide (technical name: N-[4-(1 H-imidazol-4-yl)butyl]-N'- methylthiourea, CAS Registry Number: 55720-27-9), clobenpropit (technical name: [(4-chlorophenyl)methyl]-3-(
  • H 3 antagonists Certain benzamidines and benzylamidines as H 3 antagonists have been described by R. Aslanian et al, Bioorganic & Medicinal Chemistry, 8, 2263- 2268 (1998). Other compounds can readily be evaluated to determine activity at H 3 receptors by known methods, including, for example, the guinea pig brain membrane assay and the guinea pig neuronal ileum contraction assay, both of which are described in U.S. patent 5,352,707. Another useful assay utilizes rat brain membranes and is described by West et al, "Identification of Two H3-Histamine Receptor Subtypes", Molecular Pharmacology, 33, 610-613 (1990). Numerous chemical substances are known to have histamine H, receptor antagonist activity.
  • H 1 receptor antagonists useful in the practice of the present invention include, without limitation, astemizole, ceterizine, azatadine, azelastine, acrivastine, brompheniramine, chlorpheniramine, clemastine, cyclizine, carebastine, cyproheptadine, carbinoxamine, descarboethoxyloratadine (also known as desloratadine or "DCL" ), doxylamine, dimethindene, ebastine, epinastine, efletirizine, fexofenadine, hydroxyzine, ketotifen, loratadine, levocabastine, meclizine, mizolastine, mequitazine, mianserin, noberas
  • this invention discloses a method for treatment of asthma, allergic rhinitis, and other allergic disorders, sneezing, itching runny nose, nasal congestion, redness of the eye, tearing, itching of the ears or palate, wheezing, sinusitis, and coughs associated with postnasal drip symptoms in a mammalian organism in need of such treatment comprising administering a pharmaceutical composition which comprises the neurokinin antagonist, H 3 antagonist and the H, antagonist as described above.
  • the active ingredients will typically be administered in admixture with suitable pharmaceutical diluents, excipients or carriers (collectively referred to herein as carrier materials) suitably selected with respect to the intended form of administration, i.e. oral tablets, capsules (either solid-filled, semi-solid filled or liquid filled), powders for constitution, oral gels, elixirs, dispersible granules, syrups, suspensions, and the like, and consistent with conventional pharmaceutical practices.
  • suitable pharmaceutical diluents, excipients or carriers collectively referred to herein as carrier materials
  • suitable pharmaceutical diluents, excipients or carriers suitably selected with respect to the intended form of administration, i.e. oral tablets, capsules (either solid-filled, semi-solid filled or liquid filled), powders for constitution, oral gels, elixirs, dispersible granules, syrups, suspensions, and the like, and consistent with conventional pharmaceutical practices.
  • the active drug component may be combined with any oral non-toxic pharmaceutically acceptable inert carrier, such as lactose, starch, sucrose, cellulose, magnesium stearate, dicalcium phosphate, calcium sulfate, talc, mannitol, ethyl alcohol (liquid forms) and the like.
  • suitable binders, lubricants, disintegrating agents and coloring agents may also be incorporated in the mixture.
  • Powders and tablets may be comprised of from about 5 to about 95 percent inventive composition.
  • Suitable binders include starch, gelatin, natural sugars, corn sweeteners, natural and synthetic gums such as acacia, sodium alginate, carboxymethylcellulose, polyethylene glycol and waxes.
  • lubricants there may be mentioned for use in these dosage forms, boric acid, sodium benzoate, sodium acetate, sodium chloride, and the like.
  • Disintegrants include starch, methylcellulose, guar gum and the like. Sweetening and flavoring agents and preservatives may also be included where appropriate.
  • compositions of the present invention may be formulated in sustained release form to provide the rate controlled release of any one or more of the components or active ingredients to optimize the therapeutic effects, i.e. neurokinin antagonism, antihistaminic activity and the like.
  • Suitable dosage forms for sustained release include layered tablets containing layers of varying disintegration rates or controlled release polymeric matrices impregnated with the active components and shaped in tablet form or capsules containing such impregnated or encapsulated porous polymeric matrices.
  • Liquid form preparations include solutions, suspensions and emulsions. As an example may be mentioned water or water-propylene glycol solutions for parenteral injections or addition of sweeteners and opacifiers for oral solutions, suspensions and emulsions. Liquid form preparations may also include solutions for intranasal administration.
  • Aerosol preparations suitable for inhalation may include solutions and solids in powder form, which may be in combination with a pharmaceutically acceptable carrier such as inert compressed gas, e.g. nitrogen.
  • a pharmaceutically acceptable carrier such as inert compressed gas, e.g. nitrogen.
  • a low melting wax such as a mixture of fatty acid glycerides such as cocoa butter is first melted, and the active ingredient is dispersed homogeneously therein by stirring or similar mixing. The molten homogeneous mixture is then poured into convenient sized molds, allowed to cool and thereby solidify.
  • solid form preparations which are intended to be converted, shortly before use, to liquid form preparations for either oral or parenteral administration.
  • liquid forms include solutions, suspensions and emulsions.
  • the compounds of the invention may also be deliverable transdermally.
  • the transdermal compositions may take the form of creams, lotions, aerosols and/or emulsions and can be included in a transdermal patch of the matrix or reservoir type as a re conventional in the art for this purpose.
  • the compound is administered orally.
  • the pharmaceutical preparation is in a unit dosage form.
  • the preparation is subdivided into suitably sized unit doses containing appropriate quantities of the active components, e.g., an effective amount to achieve the desired purpose.
  • the quantity of the inventive active composition in a unit dose of preparation may be generally varied or adjusted from about 0.01 milligrams to about 1 ,000 milligrams, preferably from about 0.01 to about 750 milligrams, more preferably from about 0.01 to about 500 milligrams, and typically from about 0.01 to about 250 milligrams, according to the particular application.
  • the actual dosage employed may be varied depending upon the patient's age, sex, weight and severity of the condition being treated. Such techniques are well known to those skilled in the art.
  • the human oral dosage form containing the active ingredients can be administered 1 or 2 times per day. The amount and frequency of the administration will be regulated according to the judgment of the attending clinician.
  • a generally recommended daily dosage regimen for oral administration may range from about 0.04 milligrams to about 4,000 milligrams per day, in single or divided doses.
  • Capsule - refers to a special container or enclosure made of methyl cellulose, polyvinyl alcohols, or denatured gelatins or starch for holding or containing compositions comprising the active ingredients.
  • Hard shell capsules are typically made of blends of relatively high gel strength bone and pork skin gelatins. The capsule itself may contain small amounts of dyes, opaquing agents, plasticizers and preservatives.
  • Tablet- refers to a compressed or molded solid dosage form containing the active ingredients with suitable diluents.
  • the tablet can be prepared by compression of mixtures or granulations obtained by wet granulation, dry granulation or by compaction.
  • Oral gels refer to the active ingredients dispersed or solubilized in a hydrophiliic semi-solid matrix.
  • Powders for constitution refers to powder blends containing the active ingredients and suitable diluents which can be suspended in water or juices.
  • Diluent - refers to substances that usually make up the major portion of the composition or dosage form. Suitable diluents include sugars such as lactose, sucrose, mannitol and sorbitol; starches derived from wheat, corn rice and potato; and celluloses such as microcrystalline cellulose.
  • the amount of diluent in the composition can range from about 10 to about 90% by weight of the total composition, preferably from about 25 to about 75%, more preferably from about 30 to about 60% by weight, even more preferably from about 12 to about 60%.
  • Disintegrants refers to materials added to the composition to help it break apart (disintegrate) and release the medicaments.
  • Suitable disintegrants include starches; "cold water soluble" modified starches such as sodium carboxymethyl starch; natural and synthetic gums such as locust bean, karaya, guar, tragacanth and agar; cellulose derivatives such as methylcellulose and sodium carboxymethylcellulose; microcrystalline celluloses and cross-linked microcrystalline celluloses such as sodium croscarmellose; alginates such as alginic acid and sodium alginate; clays such as bentonites; and effervescent mixtures.
  • the amount of disintegrant in the composition can range from about 2 to about 15% by weight of the composition, more preferably from about 4 to about 10% by weight.
  • Binders - refers to substances that bind or "glue” powders together and make them cohesive by forming granules, thus serving as the "adhesive" in the formulation. Binders add cohesive strength already available in the diluent or bulking agent.
  • Suitable binders include sugars such as sucrose; starches derived from wheat, corn rice and potato; natural gums such as acacia, gelatin and tragacanth; derivatives of seaweed such as alginic acid, sodium alginate and ammonium calcium alginate; cellulosic materials such as methylcellulose and sodium carboxymethylcellulose and hydroxypropylmethylcellulose; polyvinylpyrroiidone; and inorganics such as magnesium aluminum silicate.
  • the amount of binder in the composition can range from about 2 to about 20% by weight of the composition, more preferably from about 3 to about 10% by weight, even more preferably from about 3 to about 6% by weight.
  • Lubricant - refers to a substance added to the dosage form to enable the tablet, granules, etc. after it has been compressed, to release from the mold or die by reducing friction or wear.
  • Suitable lubricants include metallic stearates such as magnesium stearate, calcium stearate or potassium stearate; stearic acid; high melting point waxes; and water soluble lubricants such as sodium chloride, sodium benzoate, sodium acetate, sodium oleate, polyethylene glycols and d'l-leucine. Lubricants are usually added at the very last step before compression, since they must be present on the surfaces of the granules and in between them and the parts of the tablet press.
  • the amount of lubricant in the composition can range from about 0.2 to about 5% by weight of the composition, preferably from about 0.5 to about 2%, more preferably from about 0.3 to about 1.5% by weight.
  • Suitable glidents include silicon dioxide and talc.
  • the amount of glident in the composition can range from about 0.1% to about 5% by weight of the total composition, preferably from about 0.5 to about 2% by weight.
  • Coloring agents - excipients that provide coloration to the composition or the dosage form.
  • excipients can include food grade dyes and food grade dyes adsorbed onto a suitable adsorbent such as clay or aluminum oxide.
  • the amount of the coloring agent can vary from about 0.1 to about 5% by weight of the composition, preferably from about 0.1 to about 1%.
  • Bioavailability - refers to the rate and extent to which the active drug ingredient or therapeutic moiety is absorbed into the systemic circulation from an administered dosage form as compared to a standard or control.
  • Conventional methods for preparing tablets are known. Such methods include dry methods such as direct compression and compression of granulation produced by compaction, or wet methods or other special procedures. Conventional methods for making other forms for administration such as, for example, capsules, suppositories and the like are also well known.

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  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pulmonology (AREA)
  • Otolaryngology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Cette invention concerne une composition pharmaceutique permettant de traiter la rhinite allergique, l'asthme ainsi que les troubles apparentés. Dans un mode de réalisation, cette composition comprend une combinaison des éléments suivants dans des quantités suffisantes pour avoir un effet thérapeutique: au moins un antagoniste de neurokinine, au moins un antagoniste de H3 et au moins un antagoniste de H1.
PCT/US1999/021437 1998-10-09 1999-10-06 Composition et procede pour le traitement d'allergies WO2000021512A2 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP2000575488A JP2002527381A (ja) 1998-10-09 1999-10-06 アレルギー性疾患を処置するための組成物および方法
EP99949707A EP1117405A2 (fr) 1998-10-09 1999-10-06 Composition et procede pour le traitement d'allergies
CA002346227A CA2346227A1 (fr) 1998-10-09 1999-10-06 Composition et procede pour le traitement d'allergies
AU62526/99A AU6252699A (en) 1998-10-09 1999-10-06 Composition and method for treating allergic diseases

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US16960898A 1998-10-09 1998-10-09
US09/169,608 1998-10-09

Publications (2)

Publication Number Publication Date
WO2000021512A2 true WO2000021512A2 (fr) 2000-04-20
WO2000021512A3 WO2000021512A3 (fr) 2000-07-06

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JP (1) JP2002527381A (fr)
CN (1) CN1329490A (fr)
AR (1) AR020740A1 (fr)
AU (1) AU6252699A (fr)
CA (1) CA2346227A1 (fr)
CO (1) CO5140078A1 (fr)
MY (1) MY130725A (fr)
PE (1) PE20001097A1 (fr)
WO (1) WO2000021512A2 (fr)

Cited By (5)

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Publication number Priority date Publication date Assignee Title
WO2004069338A1 (fr) * 2003-01-31 2004-08-19 Schering Corporation Utilisation de combinaisons d'antagonistes du recepteur h1 et h3 de l'histamine pour la preparation d'un medicament destine au traitement d'etats cutanes et oculaires d'origine allergique
US7300941B2 (en) * 2000-10-17 2007-11-27 Schering Corporation Non-imidazole compounds
WO2008090117A1 (fr) 2007-01-24 2008-07-31 Glaxo Group Limited Nouvelles compositions pharmaceutiques
US9649303B2 (en) 2008-05-23 2017-05-16 Mastcell Pharmaceuticals, Inc. Methods and treatment for allergies and inflammation associated with gastrointestinal diseases
CN111836633A (zh) * 2018-01-31 2020-10-27 扎罗德克斯治疗有限公司 新的用途

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PE20020324A1 (es) * 2000-10-06 2002-06-18 Boehringer Ingelheim Int Nuevas composiciones farmaceuticas que contienen epinastina y pseudoefedrina
DE102012102417A1 (de) 2012-03-21 2013-09-26 Balluff Gmbh Identifikationssystem
CN116496205A (zh) * 2022-05-06 2023-07-28 成都施贝康生物医药科技有限公司 一种卡瑞斯汀的盐及其用途

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WO1996006094A1 (fr) * 1994-08-25 1996-02-29 Merrell Pharmaceuticals Inc. Nouvelles piperidines substituees utiles pour le traitement d'affections allergiques
WO1998006394A1 (fr) * 1996-08-16 1998-02-19 Schering Corporation Traitement des reponses allergiques des voies aeriennes superieures a l'aide d'une combinaison d'antagonistes des recepteurs de l'histamine
WO1998018785A1 (fr) * 1996-10-31 1998-05-07 Schering Corporation Derives d'oximes substitues convenant comme antagonistes de la neurokinine

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EP0625509A1 (fr) * 1993-05-17 1994-11-23 Zeneca Limited Dérivés de pipéridine N-alkyl-substitués présentant une activité antagoniste des récepteurs de neurokinines
WO1996006094A1 (fr) * 1994-08-25 1996-02-29 Merrell Pharmaceuticals Inc. Nouvelles piperidines substituees utiles pour le traitement d'affections allergiques
WO1998006394A1 (fr) * 1996-08-16 1998-02-19 Schering Corporation Traitement des reponses allergiques des voies aeriennes superieures a l'aide d'une combinaison d'antagonistes des recepteurs de l'histamine
WO1998018785A1 (fr) * 1996-10-31 1998-05-07 Schering Corporation Derives d'oximes substitues convenant comme antagonistes de la neurokinine

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Title
KUDLACZ E ET AL: "A role for histamine and substance P in immediate allergic responses in guinea pig airways: characterization of MDL 108,207DA, a dual H1 /NK-1 receptor antagonist." INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, (1998 FEB) 115 (2) 169-78., XP000885972 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7300941B2 (en) * 2000-10-17 2007-11-27 Schering Corporation Non-imidazole compounds
WO2004069338A1 (fr) * 2003-01-31 2004-08-19 Schering Corporation Utilisation de combinaisons d'antagonistes du recepteur h1 et h3 de l'histamine pour la preparation d'un medicament destine au traitement d'etats cutanes et oculaires d'origine allergique
WO2008090117A1 (fr) 2007-01-24 2008-07-31 Glaxo Group Limited Nouvelles compositions pharmaceutiques
US9649303B2 (en) 2008-05-23 2017-05-16 Mastcell Pharmaceuticals, Inc. Methods and treatment for allergies and inflammation associated with gastrointestinal diseases
CN111836633A (zh) * 2018-01-31 2020-10-27 扎罗德克斯治疗有限公司 新的用途

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JP2002527381A (ja) 2002-08-27
WO2000021512A3 (fr) 2000-07-06
MY130725A (en) 2007-07-31
EP1117405A2 (fr) 2001-07-25
CN1329490A (zh) 2002-01-02
AU6252699A (en) 2000-05-01
CA2346227A1 (fr) 2000-04-20
PE20001097A1 (es) 2000-10-31
CO5140078A1 (es) 2002-03-22
AR020740A1 (es) 2002-05-29

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